Trifluoroacetic acid → 2-(6-fluoro-1-(3-hydroxybutyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246778

반응식

HRID 246778 반응식
[Si]([O:8][CH2:9][C:10]([NH:13][C:14]([C:16]1[C:20]2=[N:21][C:22]([C:25]3[C:33]4[C:28](=[CH:29][C:30]([F:34])=[CH:31][CH:32]=4)[N:27]([CH2:35][CH2:36][CH:37]([OH:39])[CH3:38])[N:26]=3)=[CH:23][N:24]=[C:19]2[N:18](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:17]=1)=[O:15])([CH3:12])[CH3:11])(C(C)(C)C)(C)C.FC(F)(F)C(O)=O>ClCCl>[F:34][C:30]1[CH:29]=[C:28]2[C:33]([C:25]([C:22]3[N:21]=[C:20]4[C:16]([C:14]([NH:13][C:10]([CH3:11])([CH3:12])[CH2:9][OH:8])=[O:15])=[CH:17][NH:18][C:19]4=[N:24][CH:23]=3)=[N:26][N:27]2[CH2:35][CH2:36][CH:37]([OH:39])[CH3:38])=[CH:32][CH:31]=1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 71279489N-(1-(tert-Butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1-(3-hydroxybutyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

생성물 1

HCID 712797812-(6-fluoro-1-(3-hydroxybutyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide수율 45%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a stirred solution of N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1-(3-hydroxybutyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide in dichloromethane (2 mL) was added drop-wise trifluoroacetic acid (1 mL) at room temperature and the reaction mixture was stirred for 1 hour. The solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and washed with NaHCO3 (aqueous), The organic layer was concentrated, and the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 36% acetonitrile/64% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 42% acetonitrile/58% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.) to give 2-(6-fluoro-1-(3-hydroxybutyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (10 mg, 45% over three steps) as a white solid. LCMS: (M+H)+=441; 1H NMR (300 MHz, CD3OD): δ 9.15 (s, 1H), 8.58 (dd, 1H, J1=9. Hz, J2=5.4 Hz), 8.29 (s, 1H), 7.42 (d, 1H, J=7.8 Hz), 7.10 (d, 1H, J=7.2 Hz), 4.62-4.56 (m, 2H), 3.82 (s, 2H), 3.76 (brs, 1H), 2.19-2.13 (m, 2H), 2.04-1.99 (m, 2H), 1.55 (s, 6H), 1.22 (d, 3H, J=6.3 Hz).

후처리

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in dichloromethane
  3. washwashed with NaHCO3 (aqueous)
  4. concentrationThe organic layer was concentrated
  5. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  6. wait36% acetonitrile/64% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 42% acetonitrile/58% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.

출처 및 근거

ORD 기록
ord-d3c0091723fe48c8a404090691159d31
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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